Objective To investigate the role of alveolar macrophages ( AMs ) in airway inflammation of smoke-induced COPD rat model and its possible regulating mechanism. Methods Twelve Wistar rats were randomly divided into a COPD group and a control group. The rat model of COPD was established with smoke exposure and LPS intrathacheal instillation. Bronchoalveolar lavage fluid ( BALF)was collected for measurement of total and differential cell counts. Then AMs were isolated and identified byimmunofluorescence. Western blot was employed to analyze the cytoplasmic and nuclear NF-κB p65 expression of AMs. The concentrations of TNF-α,macrophage inflammatory protein 2 ( MIP-2) and IL-10 in cell culture supernatantwere assayed by ELISA.Results The scores of bronchitis and mean liner intercepts in the COPD group were significantly higher than those in the control group [ 4. 33 ±1. 16 vs. 1. 33 ±0. 58,P =0. 016; ( 168. 77 ±11. 35) μm vs. ( 93. 61 ±4. 16) μm, P = 0. 000) ] . The total cell count in BALF of the COPD group was significantly higher than that in the control group ( P lt; 0. 05) , and the AMs and neutrophils were predominant [ ( 72. 00 ±2. 22) % and ( 18. 29 ±8. 34) % ] . The cytoplasmic NF-κB p65 expression of AMs in the COPD group was significantly lower , while the nuclear NF-κB p65 expression was significantly higher ( P lt; 0. 05) compared with the control group. The ELISA results showed that the concentrations of TNF-αand MIP-2 in culture supernatant of AMs in the COPD group were significantly higher than those in the control group ( P lt;0. 05) , while the concentration of IL-10 was not significantly different between the two groups ( P gt;0. 05) . Conclusions COPD rat model was established successfully with smoke exposure and LPS intratracheal instillation with a profile of macrophage-based chronic inflammation and increased secretion of TNF-αand MIP-2. The mechanismis closely related to activation of NF-κB.
Chronic airway diseases constitute the majority of mortality of respiratory diseases in China. The 2017 Global Initiative for Chronic Obstructive Lung Disease has proposed a novel scheme for classification of disease severity. The mainstream for chronic obstructive pulmonary disease (COPD) management has shifted to the combination of long acting β2 agonists (LABA) and long acting muscarinic cholinergic antagonists instead of inhaled corticosteroid and LABA. Tiotropium was effective in early COPD with little or even without symptoms. The manangement strategy on COPD may be moving to the upper stream (early intervention). Greater interest has been focusing on clinical phenotyping and inflammatory pathways in asthma. The greater understanding of the pathogenesis of asthma has been associated with the clinical trial progress which suggests that multiple medications targeting at Th2 pathways may provide benefits for implementing personalized therapy. Medications targeting at neutrophilic airway inflammation and blockade of KIT pathways are expected to provide novel rationales for managing asthma with different phenotypes. There has been a considerable progress in bronchiectasis research in China, particularly in terms of etiology, bacteriology and clinical phenotying investigations. The establishment of bronchiectasis research centers in China may help better understanding of the pathogenesis of bronchiectasis, thus identifying potential targets for intervention, which may provide crucial rationale for future intervention to improve the long-term prognosis.
Objective To survey the prevalence of coexisting chronic obstructive pulmonary disease ( COPD) and chronic heart failure in Chengdu communities. Methods A cross-sectional study was performed in the population aged over 40 years in eight communities of Chengdu city. The subjects were selected by stratified cluster random sampling. Using the same protocol and questionnaire, all participants underwent medical history taking, physical examination and spirometry. Results Of 354 participating patients with a diagnosis of COPD, 74 ( 20. 90% ) cases were complicated with chronic heart failure. The prevalence of chronic heart failure in COPD in male was significantly higher than that in female ( 22. 69%vs. 18. 12% , P lt; 0. 05) . The major causes of chronic heart failure were hypertension ( 31. 64% ) , ischaemic heart disease ( 18. 93% ) , chronic pulonary heart disease ( 17. 51% ) and diabetes ( 11. 86% ) .Conclusions The prevalence of coexisting COPD and chronic heart failure in Chengdu city is significantly higher than the average level of the whole country, which warrant more attention in prevention and treatment of COPD in communities.
Objective To investigate the phenotyping of COPD by cluster analysis and evaluate the value of this method.Methods 168 COPD patients were enrolled from Beijing Tongren Hospital. Demographic and clinical data, such as, sex, age, body mass index ( BMI) , smoking index, course of disease,exacerbation rate, and comorbidities were collected. Pulmonary function test, emphysema scoring by HRCT,dyspnea by MMRC score, COPD assessment test ( CAT) score, six-minute walk test were performed for each patient during the stable stage. Cluster analysis was conducted using SPSS 13. 0. Results According to the GOLD criteria,5, 75, 75, and 13 patients were classified into GOLD stage 1, 2, 3, and 4, respectively. There was no difference among different stages in sex distribution, BMI, smoking index, hypertension, and cerebral infarction incidence( P gt; 0. 05) , but the differences in age, disease course, dyspnea score, six-minute walk distance, BODE score, CAT score, coronary heart disease, exacerbation rate, and HRCT emphysema visual score were significant( P lt;0. 05) . By cluster analysis,168 patients were finally classified into three groups:younger/mild, older/ severe, and older/moderate. The patients with the same GOLD stage appeared indifferent clusters and the patients belonging to different GOLD stages could be in the same cluster. There were significant differences among three groups in age, BMI, exacerbation rate, dyspnea score, CAT score, and comorbidities. The result showed that HRCT emphysema visual score was also an important index todifferentiate clusters, suggesting that emphysema was an important phenotype of COPD. Conclusions Cluster analysis can classify homogeneous subjects into the same cluster, and heterogeneous subjects into different clusters. The results suggest that COPD phenotyping by cluster analysis is clinically useful and significant.
Objective To systematically evaluate the risk factors for secondary respiratory failure (RF) on chronic obstructive pulmonary disease (COPD), so as to provide evidence for formulating prevention and control strategies. Methods PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP databases and SinoMed were searched for articles published from the dates of establishment of databases to August 2021. To collect the relevant case-control studies or cohort studies on the risk factors of secondary RF in patients with COPD. The patients were divided into two groups, RF group and non RF group. Meta-analysis was carried out with RevMan 5.3 software after selecting literature, extracting data and evaluating quality according to inclusion and exclusion criteria. Results A total of 16 case-control studies involving 2 417 patients were included. There were 856 cases in RF group and 1 561 cases in non RF group. The results of meta-analysis showed that age [mean difference (MD)=0.58 years, 95% confidence interval (CI) (0.18, 0.97) years, P=0.004], number of acute attacks per year [MD=2.68 times, 95%CI (2.58, 2.78) times, P<0.001], number of acute attacks per year over 3 [odds ratio (OR)=3.37, 95%CI (2.40, 4.73), P<0.001], serum albumin level [MD=−2.93 g/L, 95%CI (−3.92, −1.94), P<0.001], serum uric acid [MD= −59.91 mmol/L, 95%CI (−66.57, −53.25) mmol/L, P<0.001], nosocomial infection [OR=4.53, 95%CI (3.44, 5.98), P<0.001], no-inhaled glucocorticoid [OR=3.63, 95%CI (2.95, 4.48), P<0.001], acid-base imbalance [OR=13.22, 95%CI (10.14, 17.23), P<0.001], COPD very serious [OR=1.82, 95%CI (1.50, 2.21), P<0.001], cardiovascular disease [OR=2.73, 95%CI (1.99, 3.74), P<0.001], kidney disease [OR=3.62, 95%CI (2.67, 4.90), P<0.001] were risk factors for RF in COPD. Sensitivity analysis showed that the results of meta-analysis were stable. Conclusion According to the results of meta-analysis, the risk factors of secondary RF in COPD can be identified in time and preventive measures can be taken to effectively reduce the incidence of aspiration failure and improve the prognosis and outcome of patients.
Objective To investigate the effects of simvastatin on pulmonary function and vascular endothelial growth factor ( VEGF) levels in induced sputumof patients with COPD exacerbation( AECOPD) .Methods Thirty-eight patients with AECOPD were divided into two groups randomly, ie. a routine medical treatment( RT) group( n =30) and a routine + statin medical treatment( RST) group( n =28) . The VEGF levels in serumand induced sputum were detected by ELISA on the first day and after a week treatment in hospital, respectively. Meanwhile, the pulmonary function measurements were performed. Results There were no significant differences in the pulmonary function ( FEV1% pred and FEV1 /FVC) and VEGF levels in induced sputumbetween the two groups before treatment( P gt;0. 05) . The RT group showed no significantchanges in any parameters before and after a week treatment( P gt; 0. 05) . FEV1% pread, FEV1 /FVC and VEGF levels in induced sputum in the RST group after a week treatment significantly increased compared with those before treatment and the RT group( P lt;0. 01, P lt;0. 01, P lt;0. 05) . But There were no significant differences in serumVEGF levels between the two groups before and after a week treatment. The VEGF levels in induced sputum were positively correlated to FEV1% pread and FEV1 /FVC after a week treatment( r =0. 430, P lt;0. 05; r = 0. 388, P lt; 0. 05) . Conclusions Simvastatin may reduce the decline in pulmonary function and decrease the levels of VEGF in induced sputum of patients with AECOPD. Improvement in pulmonary function may be related to down-expression of lung VEGF
Objective To investigate whether ADAM33 ( A disintegrin and metalloproteinase 33) gene polymorphismhas effect on the airway inflammation of COPD. Methods A total of 312 COPD patients were recruited for this study. Four polymorphic loci ( T2, T1, S2, and Q-1) of ADAM33 were selected for genotyping by using the polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) method. Total and differential cell counts, contents of TNF-α, IL-6, IL-8, and VEGF in induced sputumwere detected. The relationship between genotypes and inflammatory reaction was analyzed. Results On locus T2, the cell counts and content of TNF-αin induced sputum increased significantly in the carriers with GG genotype than those with AA and AG genotypes ( Plt;0.01 and Plt;0.05) . On locus T1, the lymphocyte counts in induced sputumincreased significantly in the carriers with GG genotype than those with AA and AG genotypes ( Plt;0.05) ; but the content of IL-8 in induced sputumwas higher in AA and AG genotypes ( Plt;0.05) . On locus Q-1, the contents of VEGF and IL-8 in induced sputum increased significantly in the carriers with GG genotype than those with AA and AG genotypes (Plt;0.05) . On locus S2, the total cell counts in induced sputumincreased significantly in the carriers with GG genotype than those with CC and CG genotypes ( Plt;0.05) , and the content of IL-8 in induced sputum increased significantly in GG genotype ( Plt;0.01 ) . Conclusion These results suggest that ADAM33 polymorphism may participate the pathogenesis of COPD by promoting airway inflammation.
【Abstract】 Objective To observe the plasma levels of adiponectin and interleukin-17 ( IL-17) in patients with chronic obstructive pulmonary disease ( COPD) at acute exacerbation or stable stage, and analyze their relationship. Methods Sixty male COPD patients with normal weight ( with BMI range of 18. 5-24. 9 kg/m2 ) were enrolled, including 30 patients with acute exacerbations of COPD ( AECOPD) and 30 patients with stable COPD. Twenty healthy nonsmoking male volunteers were included as controls. The plasma levels of adiponectin and IL-17 as well as lung function ( FEV1% pred and RV% pred) were measured in all subjects. Results The concentrations of adiponectin and IL-17 were significantly higher in the AECOPD patients than those of the patients with stable COPD and the contro1s ( P lt; 0. 001) . Theconcentrations of adiponectin and IL-17 were significantly higher in the patients with stable COPD than those of the controls ( P lt;0. 01) . Adiponectin was positively correlated with IL-17 in the AECOPD patients ( r =0. 822, P lt;0. 001) and in the patients with stable COPD ( r =0. 732, P lt;0. 001) . Adiponectin was positivelycorrelated with RV% pred in the AECOPD patients ( rs = 0. 764, P lt;0. 001) and in the patients with stable COPD ( rs =0. 967, P lt;0. 001) . There was no significant relationship between adiponectin and FEV1% pred ( P gt;0. 05) . Conclusions The plasma level of adiponectin in COPD patients is elevated which is relatedwith excessive inflation of lung. Adiponectin may be involved in the process of inflammation in COPD as a new pro-inflammatory cytokine.
Objective To observe the effects of salmeterol / fluticasone combined with tiotropium in the treatment of sever to very sever COPD. Methods Eighty patients with severe to very severe stable COPD were recruited from outpatient of Central Hospital of Cangzhou between May 2008 and October 2009. The subjects were randomly divided into a salmeterol /fluticasone group and a combination group. The salmeterol / fluticasone group received salmeterol / fluticasone propionate, and the combination group received the combination therapy of tiotropium and salmeterol / fluticasone propionate. All patients had received the treatment for 12 months. At baseline and at the end of 1-month, 3-month, 6-month, 12-month, lung function ( FEV1 , IC and FVC) , six-minute walk distance and the St. George’s Respiratory Questionnaire ( SGRQ) score were assessed. The number of exacerbations and the time to the first exacerbation were also recorded. Results At every visit, lung function ( FEV1 , IC and FVC) , six-minute walk distance and the SGRQ score were improved in both groups compared with baseline ( Plt;0. 05) , especially in the combination group ( Plt;0.05) . Compared with the salmeterol /fluticason, the combination therapy with tiotropium significantly decreased the incidence of exacerbations and prolonged the time to the first exacerbation ( Plt;0.05) . And there was no significant difference between two groups in adverse effects ( Pgt;0.05) . Conclusions The combination therapy with salmeterol / fluticasone propionate and tiotropium was superior to salmeterol / fluticasone propionate in treatment of sever to very severe stable COPD patients in improving lung function, exercise tolerance, and quality of life, without additional adverse effects.
Objective To explore the daytime variables which are predictive to nocturnal hyoxemia among COPD patients unqualified for long-term oxygen therapy ( LTOT) . Methods Forty-eight stable COPD patients with SaO2≥90% were enrolled in this study and regarded as patients unqualified for LTOT. All patients underwent lung function examination during daytime. Their nocturnal oxygen saturation was monitored with overnight pulse oximetry ( OPO) . ResultsDaytime oxygen saturation was positively correlated with nocturnal mean SaO2 ( r =0. 79, P lt;0. 0001) , and negatively correlated with time spend with saturation below 90% ( TB90) ( r = - 0. 75, P lt; 0. 0001) . No significant relationship was found between lung function parameters and nocturnal SaO2 . The patients with daytime oxygen saturation between 90% and 95% were more likely to have lower nocturnal oxygen saturation and longer TB90 ( P lt;0. 05) .Conclusions Daytime oxygen saturation may effectively predict the occurrence of nocturnal hyoxemia in stable COPD patients unqualified for LTOT. To reduce COPD complications and improve prognosis, we suggest a relative indication of LTOT for patients with daytime oxygen saturation between 90% and 95% and with nocturnal hyoxemia.